Document Detail

Therapeutic time window in the penumbra during permanent focal ischemia in rats: changes of free fatty acids and glycerophospholipids.
MedLine Citation:
PMID:  10874689     Owner:  NLM     Status:  MEDLINE    
To better define a therapeutic time window for reducing the extent of damage in ischemic penumbra, the time courses of changes in the glycerophospholipid and free fatty acid (FFA) levels were determined in the rat cerebral cortex following induction of the permanent focal ischemia. Focal ischemia induced a biphasic increase in FFA levels in the cerebral cortex, which had been recognized as the ischemic penumbra during the early stages after permanent occlusion of the middle cerebral artery (MCA). The first increase in FFA levels, in which the polyunsaturated fatty acid (PUFA) contained a large number of arachidonic acid (C20:4) molecules, began at 30 min and reached a peak at 1 h, followed by transient return to each sham level 2-6 h after the onset of MCA occlusion. Thereafter, the delayed increase in FFA levels, showing more increases of docosahexaenoic acid (C22:6) molecules than the C20:4 in PUFA compositions, occurred at 24 h. In contrast, the levels of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) decreased rapidly at 30 min of ischemia and returned transiently to each sham level at 1-6 h. The levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE), including polyphosphoinositides (PIPs), began to decrease significantly during the late stages, i.e., 24 h after induction of ischemia. These results suggest that the time-dependent changes in FFA and PIPs levels during the early stages of ischemia (until 6 h after induction) might be an important determinant of the subsequent neuronal death in the ischemic penumbra and that the breakdown of glycerophospholipids in the later stages after the induction of focal ischemia was associated with the development of infarction in the cerebral cortex.
K Narita; M Kubota; M Nakane; S Kitahara; T Nakagomi; A Tamura; H Hisaki; H Shimasaki; N Ueta
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neurological research     Volume:  22     ISSN:  0161-6412     ISO Abbreviation:  Neurol. Res.     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-10-19     Completed Date:  2000-10-19     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7905298     Medline TA:  Neurol Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  393-400     Citation Subset:  IM    
Department of Neurosurgery, Teikyo University School of Medicine, Tokyo, Japan.
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MeSH Terms
Brain Ischemia / metabolism*,  therapy*
Cerebral Cortex / blood supply,  metabolism
Cerebral Revascularization
Docosahexaenoic Acids / metabolism
Fatty Acids, Nonesterified / metabolism*
Fatty Acids, Unsaturated / metabolism
Infarction, Middle Cerebral Artery / metabolism,  therapy
Phosphatidylinositol 4,5-Diphosphate / metabolism*
Rats, Sprague-Dawley
Time Factors
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Fatty Acids, Unsaturated; 0/Phosphatidylinositol 4,5-Diphosphate; 25167-62-8/Docosahexaenoic Acids

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